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Objective: To report the clinical manifestations, response to antiviral treatment, and long-term visual outcomes of cytomegalovirus endotheliitis in a Canadian population., Design: Retrospective case series., Participants: A total of 9 eyes of 7 patients referred to a cornea subspecialty clinic in a major Canadian centre with corneal endotheliitis., Methods: A retrospective review of all patients presenting with corneal endotheliitis to 1 corneal surgeon was completed. Patients underwent anterior chamber biopsy with positive cytomegalovirus polymerase chain reaction. All patients received systemic valganciclovir for a minimum of 3 months. Primary outcomes included visual acuity, intraocular pressure control, medication dependence, and corneal status., Results: The average follow-up was 76.4 ± 11.8 months. Two patients had bilateral disease. Corneal manifestations included linear, disciform, and circinate patterns of endotheliitis. Best-corrected visual acuity improved from a mean of 0.48 ± 0.19 logMAR at presentation to 0.24 ± 0.11 logMAR at last follow-up. Intraocular pressure decreased from a peak of 35 ± 3.1 mm Hg to 14.2 ± 4.3 mm Hg. Antiglaucoma medications were reduced from 2.6 ± 0.45 to 0.89 ± 0.29 agents. Two eyes required endothelial transplantation. Valganciclovir therapy was well tolerated by all patients; at the time of last follow-up, all patients were stable on low-dose valganciclovir at an average dose of 1395 mg per week., Conclusions: Cytomegalovirus is an uncommon but clinically significant cause of corneal endotheliitis that must be considered in the differential diagnosis of corneal endotheliitis, even in the immunocompetent population. Our results support prior findings that this entity responds robustly to oral valganciclovir and demonstrate for the first time the efficacy of chronic low-dose antiviral maintenance therapy., (Copyright © 2022. Published by Elsevier Inc.)